4-Bromo-2-methoxybenzardehyde is useful as an intermediate in the chemical industry.
Syntheses are described in the literature to yield 4-bromo-2-methoxybenzaldehyde. For example, 4-bromo-2-methoxybenzaldehyde has already been synthesized through the formylation of meta bromo anisole, however the selectivity is low (J. Org. Chem. 2007, 72, 9786 & European Journal of Medicinal Chemistry, 1986, 21(5), 397-402). It is also described as being synthesized through metal halogen exchange between 1,4-dibromo 2-methoxybenzene and butyl lithium in cryogenic conditions, i.e., at −78° C. in diethyl ether, which is not a suitable solvent for large scale (Tetrahedron 2005, 61, 6590-6595). On the other hand, lida et al. reported the synthesis of the intermediate 2-fluoro-4-bromobenzaldehyde via metal halogen exchange between 1,4 dibromo-2-fluorobenzene and tributylmagnesium ate complex, which needs to be prepared from butyl magnesium chloride and butyl lithium, followed by the formylation with DMF in 92% yield (Tetrahedron Letters 2001, 42, 4841). Luo Zhiyong et al described the preparation of 4-bromo-2-methoxybenzaldehyde from 2-fluoro-4-bromobenzaldehyde through a SNAr reaction in the presence of sodium methoxide in a modest yield of 38%.
It would be beneficial to the pharmaceutical industry to have processes for producing 4-bromo-2-methoxybenzaldehyde that have good selectivity and that do not require the use of cryogenic conditions.